Antipsychotic drugs may be harmful for people with Parkinson's

Antipsychotic drugs that are commonly prescribed for people with Parkinson's disease may be causing additional harm, says research reported in JAMA Neurology.

Physicians may prescribe antipsychotics for some patients with Parkinson's.

Parkinson's disease is a neurological disorder primarily affecting older people. Around 1 million Americans are estimated to be living with Parkinson's, and physicians diagnose 60,000 new cases each year, according to the Parkinson's Disease Foundation.

Parkinson's causes tremors, rigidity and difficulty walking in the early stages; in time, it can lead to cognitive decline.

Research has shown that up to 60% of patients with Parkinson's experience psychosis and 80% develop dementia. Antipsychotics, such as quetiapine, are commonly prescribed.

Potential adverse effects of antipsychotic drugs include reduced alertness, a higher risk of diabetes and heart disease, low blood pressure and, in the long term, movement disorders that resemble those seen in Parkinson's.

Antipsychotic drug packages carry warnings for patients with dementia

Since 2005, the Food and Drug Administration (FDA) have required antipsychotic drug packaging to carry "black box" warnings, initially due to evidence that they could lead to strokes among users.

Previous studies have suggested that psychotic drugs may cause higher rates of mortality among patients with dementia, and the FDA warning notes the risk to patients with dementia.

Most people with dementia have Alzheimer's disease, but there are other forms of dementia, and one of these occurs in around 80% of individuals with Parkinson's, usually some years after diagnosis.

In 2011, Dr. Daniel Weintraub, senior author of the current study, and colleagues found that despite these warnings, there was little action to reduce prescriptions of antipsychotic for patients with Parkinson's.

To investigate further, Dr. Weintraub and researchers at the Perelman School of Medicine at the University of Pennsylvania, the University of Michigan Medical School and the Philadelphia and Ann Arbor Veterans Affairs (VA) Medical Centers analyzed records, from a large Veterans Affairs database, for around 15,000 patients.

The team wanted to know whether the use of antipsychotic drugs might lead to higher mortality in all patients with Parkinson's, not just those with dementia.

Although psychosis in Parkinson's normally occurs with dementia and later-stage disease, it can manifest early on, and even when there is no dementia.

The exact cause of psychosis in Parkinson's is unclear, but it may be due to the spread of the disease to certain brain areas or the use of certain drugs for enhancing dopamine function.

Higher risk of mortality among patients with Parkinson's

The researchers compared 7,877 Parkinson's patients who received prescriptions for antipsychotic drugs at any time from 1999-2010 with a control group that did not use the drugs.

They matched participants for factors such as age, ethnicity, gender, years since diagnosis and presence of dementia.

Results showed that in the 180 days after starting antipsychotic drugs, the rate of mortality among those taking the drugs was 2.35 higher than among those who were not.

Those taking quetiapine had a 2.16 higher risk compared with no treatment; with risperidone, the risk was 2.46 times higher, with olanzapine, 2.79 times, and haloperidol was associated with a 5.08 times higher rate of mortality.

Overall, first-generation antipsychotics, such as haloperidol, appeared to entail a 50% higher relative risk of mortality than more recently developed antipsychotics - for example, risperidone and quetiapine.

While the findings imply a risk, it remains unclear why the risk is greater for certain patient groups, partly because the dataset mostly listed the cause of death as "Parkinson's disease," rather than a specific mechanism. The team hopes that a new study will reveal more details.

Dr. Weintraub calls for "careful consideration" before prescribing antipsychotics for patients with Parkinson's.

He suggests alternative approaches, such as treating other medical conditions related to psychosis, reducing the dosage of dopamine replacement treatments and managing the psychosis through means other than psychotic drugs.

He says:

"Antipsychotics should be used in these patients only when the psychosis is of clinical significance, and patients probably should not be left on these drugs long term without re-evaluation."

In a linked editorial, Dr. Mark S. Baron, of the Virginia Commonwealth University Health System in Richmond, VA, points out that: "Faced with a patient with PD [Parkinson's disease] with uncontrollable hallucinations or for that matter an elderly patient with dementia and delirium, health care professionals are confronted with a difficult situation, often with no effective and clearly safe approaches."

Dr. Baron supports the authors' call for caution and further research.

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